{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:45:03Z","timestamp":1777927503002,"version":"3.51.4"},"reference-count":78,"publisher":"SAGE Publications","issue":"15-16","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>\n                    Our objective was to test the hypothesis that structure-based identified or designed compounds exhibiting neuroprotective, antioxidant, and anti-inflammatory properties\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    will mitigate early seizures and neuropathology after traumatic brain injury (TBI)\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . The neuroprotective and anti-inflammatory effects of 11 compounds identified by computer-assisted approximations were tested\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    in neuronal microglial co-cultures. Among these, compound FBA exhibited the best neuroprotective (MAP-2, microtubule-associated-protein 2, a neuronal damage biomarker), antioxidative (nitrite production), and anti-inflammatory effects\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    (all\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.01). Consequently, its neuroprotective and antiseizure effects were assessed\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    in adult male Sprague-Dawley rats exposed to severe lateral fluid-percussion-induced TBI. Rats under continuous video-electroencephalogram monitoring received prophylactic treatment with an intraperitoneal (i.p.) injection of FBA (FBApro, 30 mg\/kg) or vehicle (VEH, 48% PEG in 0.9% saline, 3 mL\/kg) at 2 and 24 h post-TBI. Rats that developed status epilepticus received 1\u20132 additional on-demand FBA doses (FBApro+, 100 mg\/kg, i.p.) to stop epileptiform activity. FBApro treatment reduced the cortical lesion area (18.9 \u00b1 4.1 mm\n                    <jats:sup>2<\/jats:sup>\n                    ,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 7) compared with VEH treatment (24.8 \u00b1 5.7 mm\n                    <jats:sup>2<\/jats:sup>\n                    ,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 10,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.05). FBApro treatment also showed a favorable effect on the white matter by reducing plasma levels of pNF-H, a biomarker of axonal injury, compared with VEH treatment (Cohen\u2019s delta 0.657). Both FBApro (368 \u00b1 407 s) and FBApro+ (256 \u00b1 327 s) treatments reduced the average cumulative seizure duration compared with VEH (896 \u00b1 703 s, both\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.05). The FBApro+ treatment regimen also reduced the mean relative theta and alpha power and increased the mean relative gamma power in the electroencephalogram (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.05). Our data identified FBA as a novel structure-based discovered compound with promising favorable effects on structural and functional recovery after TBI.\n                  <\/jats:p>","DOI":"10.1089\/neu.2024.0070","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T12:37:21Z","timestamp":1744893441000},"page":"1433-1452","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitigation of Acute Seizures and Neuropathology after Traumatic Brain Injury by Structure-Based Discovery-Identified Drugs"],"prefix":"10.1177","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4282-0969","authenticated-orcid":false,"given":"Natallie","family":"Kajevu","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, A. I. 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